Impact of early-life ozone exposure on childhood asthma, and the modifying and synergistic effects of breastfeeding: A two-wave multi-city study of 72,135 Chinese preschool children.

Early-life ozone (O3) exposure and breastfeeding are associated with childhood asthma. However, the modifying and synergistic effects of breastfeeding on O3-asthma relationships have not been investigated. This cross-sectional study included 72,135 Chinese preschoolers from two China Children and Homes Health surveys. Individual O3 exposure during the first 1000 days was estimated at 1-km resolution. Asthma, asthma-related symptoms, and breastfeeding duration were investigated using standardized questionnaires. Generalized linear models and exposure-response curves were employed to investigate O3-asthma relationships. Multiplicative and additive interactions were used to assess the modifying and synergistic effect of breastfeeding on O3-asthma relationships, respectively. Early-life O3 exposure was associated with elevated risks of doctor-diagnosed asthma, ever asthma, and current night-cough, with odds ratios (ORs) ranging from 1.093 (95% confidence interval (CI): 1.076, 1.111) to 1.201 (95%CI: 1.165, 1.239) per 10 μg/m3 increase in O3. Sufficient breastfeeding was associated with decreased risks of doctor-diagnosed asthma, ever wheeze, current wheeze, and current night-cough, with ORs ranging from 0.749 (95%CI: 0.701, 0.799) to 0.901 (95%CI: 0.859, 0.945). Children with sufficient breastfeeding exhibited lower O3-related ORs for doctor-diagnosed asthma and ever wheeze than those with insufficient breastfeeding. Children with both insufficient breastfeeding and high O3 exposure exhibited the highest risks for doctor-diagnosed asthma, ever wheeze, current wheeze and current night-cough, with ORs ranging from 1.522 (95%CI: 1.423, 1.627) to 2.638 (95%CI: 2.481, 2.804). The synergy index revealed synergistic effects of insufficient breastfeeding and high O3 on childhood asthma and related symptoms, with SI ranging from 1.227 (95%CI: 1.098, 1.372) to 1.376 (95%CI: 1.136, 1.667). Across different periods of the first 1000 days, the modifying and synergistic effects of breastfeeding were more frequently observed during infancy and toddlerhood. Future prospective longitudinal studies and mechanistic investigations are warranted to confirm our findings and guide policy development for the prevention and control of childhood asthma.